Category Archives: Cancer

Cannabis-related cognitive impairment: a prospective evaluation of possible influences on patients with cancer during chemotherapy treatment as a pilot study.

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“In patients with cancer, the use of medical cannabis has increased significantly during the recent years. There is evidence that cannabis consumption may affect cognitive performance; however, this potential effect has not been investigated prospectively in patients with cancer to date.

We aimed to evaluate the effect of cannabis consumption on cognitive abilities as well as on symptom relief in patients with cancer during chemotherapy treatment.

RESULTS:

Improvement in executive functioning was demonstrated in the case group. In aspects of symptoms, improvement in fatigue, appetite and sleep disorder was demonstrated after cannabis consumption. Patients consuming cannabis did not differ from the control group in cognitive functioning over 3 months of use. No significant cognitive decline was observed in either group over time.

CONCLUSION:

These preliminary findings suggest that the short-term use of cannabis during chemotherapy treatment improved disease-related symptoms and did not affect cognitive skills in patients with cancer.”

 https://www.ncbi.nlm.nih.gov/pubmed/30540595
https://insights.ovid.com/crossref?an=00001813-201901000-00011

Health-related quality of life across cancer cachexia stages.

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“Cancer cachexia (CC) is common in advanced cancer and is accompanied by negative effects on health-related quality of life (HRQOL).

However, methods to identify the impact of CC on HRQOL are limited.

Finally, the use of cannabinoids in treating appetite loss was examined,

54 patients underwent cannabinoid treatment for appetite loss within a community-based, physician-lead, medical cannabis clinic.

Edmonton Symptom Assessment System (ESAS) score for lack of appetite significantly improved between baseline and follow-up after cannabinoid treatment, with no significant difference in weight.

Improvement of HRQOL via appetite stimulation, may be achieved through a multidisciplinary approach, which includes cannabinoid therapy.”

 https://www.ncbi.nlm.nih.gov/pubmed/30525763
http://apm.amegroups.com/article/view/21116

An Integrated Review of Cannabis and Cannabinoids in Adult Oncologic Pain Management.

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Pain Management Nursing

“The objective of this paper is to review the available literature regarding the use of cannabis and cannabinoids in adult oncologic pain management.

RESULTS:

The final number of articles included is nine articles. Of the nine studies reviewed, eight reviewed the effect of the cannabinoid THC on cancer pain, and one study reviewed the use of medicinally available whole plant cannabis. The following study types were included: multiple multi-center, randomized, placebo- controlled trials and two prospective observational survey studies.

RESULTS AND CONCLUSIONS:

Of the eight studies that reviewed the effect of the cannabinoid THC, five found THC to be more effective than placebo, one found THC to be more effective than placebo in American patients but ineffective in patients from other countries, and two found THC to be no more effective than placebo. The study that reviewed the effect of the whole plant cannabis found that there was a significant decrease in pain among those patients smoking cannabis.”

https://www.ncbi.nlm.nih.gov/pubmed/30527857

https://www.painmanagementnursing.org/article/S1524-9042(18)30209-1/fulltext

Cannabidiolic Acid-Mediated Interference with AP-1 Transcriptional Activity in MDA-MB-231 Breast Cancer Cells.

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“We reported that cannabidiolic acid (CBDA), a non-psychotropic constituent of fiber-type cannabis plants, down-regulates the mRNA expression of cyclooxygenase-2 (COX-2) in highly aggressive MDA-MB-231 human breast cancer cells. However, the molecular mechanism(s) underlying the CBDA suppression of COX-2 have not yet been elucidated in detail. In MDA-MB-231 cells, COX-2 expression is known to be tightly regulated by the transcriptional activity of activator protein-I (AP-1), which is composed of a heterodimer of c-Fos and c-Jun. AP-1-mediated transcriptional activity was inhibited by CBDA in a dose-dependent manner. The expression of c-fos was maintained at markedly lower levels (0.035) than basal c-jun expression levels (1.0), implicating c- fos as a limiting factor in the regulation of COX-2. Analyses indicated that CBDA abrogated the expression of c-fos mRNA without affecting c-jun. Collectively, these results suggest that CBDA abolishes the expression of COX-2 by interfering with AP-I activity in MDA-MB3-231 cells.”

https://www.ncbi.nlm.nih.gov/pubmed/30496661

miR-23b-3p and miR-130a-5p affect cell growth, migration and invasion by targeting CB1R via the Wnt/β-catenin signaling pathway in gastric carcinoma.

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“Gastric cancer (GC) is the most common malignancy and third leading cause of cancer mortality worldwide. The identification of a sensitive biomarker as well as effective therapeutic targets for the treatment of GC is of critical importance. microRNAs play significant roles in the development of cancer and may serve as promising therapeutic targets.

RESULTS:

In the present study, it was demonstrated that the cannabinoid receptor 1 (CB1R) was overexpressed, and miR-23b-3p and miR-130a-5p were downregulated, in GC cells. In addition, the results revealed that these effects are associated with malignant biological behaviors exhibited by GC cells. Furthermore, miR-23b-3p and miR-130a-5p may regulate CB1R expression via the Wnt/β-catenin signaling pathway.

CONCLUSION:

Our results suggested dysregulation of CB1R expression is closely related to the malignant biological behavior of gastric cancer cells. miRNA/CB1R-based therapy may represent a promising therapeutic strategy for the clinical treatment of GC patients.”

https://www.ncbi.nlm.nih.gov/pubmed/30498363

https://www.dovepress.com/mir-23b-3p-and-mir-130a-5p-affect-cell-growth-migration-and-invasion-b-peer-reviewed-article-OTT

Naturally occurring compounds as pancreatic cancer therapeutics.

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“Naturally occurring small molecule compounds have long been in the spotlight of pancreatic cancer research as potential therapeutics to prevent cancer progression and sensitize chemoresistant tumors. The hope is that terminal pancreatic cancer patients receiving aggressive chemotherapy can benefit from an increase in treatment efficacy without adding further toxicity by way of utilizing natural compounds. While preclinical studies on a number of natural compounds, such as resveratrol, curcumin, rapalogs and cannabinoids, show promising preclinical results, little has translated into clinical practice, though a number of other compounds hold clinical potential. Nevertheless, recent advances in compound formulation may increase the clinical utility of these compounds.”

https://www.ncbi.nlm.nih.gov/pubmed/30459936

“The combination of natural products and standard of care chemotherapy has the potential to increase quality of life and lifespan in pancreatic cancer patients, even though a number of hurdles need to be overcome for routine clinical use.”  http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=26234&path[]=81769

“Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells via Endoplasmic Reticulum Stress–Related Genes. In conclusion, results presented here show that cannabinoids exert a remarkable antitumoral effect on pancreatic cancer cells in vitro and in vivo due to their ability to selectively induce apoptosis of these cells via activation of the p8-ATF-4-TRB3 proapoptotic pathway.”  http://cancerres.aacrjournals.org/content/66/13/6748

The endocannabinoid signaling system in cancer

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Image result for trends in pharmacological sciences“Changes in lipid metabolism are intimately related to cancer. Several classes of bioactive lipids play roles in the regulation of signaling pathways involved in neoplastic transformation and tumor growth and progression.

The endocannabinoid system, comprising lipid-derived endocannabinoids, their G-protein-coupled receptors (GPCRs), and the enzymes for their metabolism, is emerging as a promising therapeutic target in cancer.

This report highlights the main signaling pathways for the antitumor effects of the endocannabinoid system in cancer and its basic role in cancer pathogenesis, and discusses the alternative view of cannabinoid receptors as tumor promoters.

We focus on new players in the antitumor action of the endocannabinoid system and on emerging crosstalk among cannabinoid receptors and other membrane or nuclear receptors involved in cancer. We also discuss the enzyme MAGL, a key player in endocannabinoid metabolism that was recently recognized as a marker of tumor lipogenic phenotype.”

https://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(13)00044-8?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0165614713000448%3Fshowall%3Dtrue

Oncology Clinicians and the Minnesota Medical Cannabis Program: A Survey on Medical Cannabis Practice Patterns, Barriers to Enrollment, and Educational Needs.

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“Medical cannabis has been available in the State of Minnesota since July 2015 through the Minnesota Medical Cannabis Program (MMCP).

Objectives: Our study aimed to delineate oncology providers’ views on medical cannabis, identify barriers to patient enrollment, and assess clinicians’ interest in a clinical trial of medical cannabis in patients with stage IV cancer.

Results: Of the 529 eligible survey participants, 153 (29%) responded to our survey; 68 respondents were registered with the MMCP. Most identified themselves as a medical oncologist or medical oncology nurse practitioner/physician assistant (n=125, 82%), and most practiced in a community setting (n=102, 67%). Overall, 65% of respondents supported the use of medical cannabis. Perceived cost and inadequate research were the highest barriers to MMCP patient enrollment. The lowest barriers included lack of health group support for allowing certification of patients and risk of social stigma. Of all respondents, 36% lacked confidence in discussing the risks and benefits of medical cannabis, and 85% wanted more education.

Conclusions: Although support for cannabis use in the cancer setting is growing, significant barriers remain. This study illustrates a clear need to give clinicians both data and education to guide their discussions about the benefits, risks, and cost considerations of using medical cannabis for cancer-related symptoms.”

https://www.ncbi.nlm.nih.gov/pubmed/30426072

https://www.liebertpub.com/doi/10.1089/can.2018.0029

Synthetic cannabinoids nano-micelles for the management of triple negative breast cancer.

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 Journal of Controlled Release

“Triple-negative breast cancer (TNBC) is a highly heterogeneous disease with poor prognosis and inadequate therapeutic outcome. This contribution reports the use of a cannabinoid derivative, WIN55,212-2 (WIN) on the growth of TNBC in a 4T1 syngeneic mouse model.

To reduce the well-known psychoactive side effects of cannabinoids, we prepared a nanomicellar formulation of WIN (SMA-WIN). In vivo biodistribution, in silico ADME predictions, anticancer activity, and psychoactive effect of WIN and SMA-WIN studies suggest that SMA-WIN formulation can reduce to greater extent tumor growth with milder psychoactive side effects when compared to free drug.

Finally, the effects of WIN and SMA-WIN in combination with doxorubicin (Doxo), an established chemotherapeutic agent for the treatment of TNBC, were investigated in vitro and in vivo. SMA-WIN in combination with Doxo showed therapeutic efficacy and was able to reduce the tumor volume of TNBC murine model drastically. Moreover, SMA-WIN, while favoring drug tumor accumulation, minimized the adverse psychoactive effects that have impeded the use of this agent in the clinic.

To our knowledge, this is the first report for the assessment of cannabinoid nanoparticles in vivo for the treatment of TNBC and its enhanced anticancer effect at low doses with Doxo. These findings suggest a new therapeutic strategy in the management of TNBC.”

https://www.ncbi.nlm.nih.gov/pubmed/30367922

https://www.sciencedirect.com/science/article/pii/S0168365918306114?via%3Dihub

Light-activatable cannabinoid prodrug for combined and target-specific photodynamic and cannabinoid therapy.

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“Cannabinoids are emerging as promising antitumor drugs. However, complete tumor eradication solely by cannabinoid therapy remains challenging. In this study, we developed a far-red light activatable cannabinoid prodrug, which allows for tumor-specific and combinatory cannabinoid and photodynamic therapy. This prodrug consists of a phthalocyanine photosensitizer (PS), reactive oxygen species (ROS)-sensitive linker, and cannabinoid. It targets the type-2 cannabinoid receptor (CB2R) overexpressed in various types of cancers. Upon the 690-nm light irradiation, the PS produces cytotoxic ROS, which simultaneously cleaves the ROS-sensitive linker and subsequently releases the cannabinoid drug. We found that this unique multifunctional prodrug design offered dramatically improved therapeutic efficacy, and therefore provided a new strategy for targeted, controlled, and effective antitumor cannabinoid therapy.”

 https://www.ncbi.nlm.nih.gov/pubmed/30334393
https://www.spiedigitallibrary.org/journals/Journal-of-Biomedical-Optics/volume-23/issue-10/108001/Light-activatable-cannabinoid-prodrug-for-combined-and-target-specific-photodynamic/10.1117/1.JBO.23.10.108001.short?SSO=1